The development of new enabling technologies is critical to improving our understanding and treatment of disease. Immunoassays, gene sequencing, and mass spectrometry represent examples of technologies that have revolutionized biomedical research by allowing the identification of biomarkers and disease pathways that could not have been discovered otherwise. We propose here a new COBRE center focused on Molecular Analysis of Disease Pathways. This Center will bring together junior and senior faculty from the physical, biological, and pharmaceutical sciences at the University of Kansas and other academic institutions in Kansas to conduct multidisciplinary research to develop and implement cutting-edge technologies for elucidating the genetic, chemical, and physical mechanisms of biological processes involved in disease. The scientific emphasis ofthe Center will be to create and implement new enabling technologies for identification of therapeutic targets. These enabling methodologies include methods for integrating next generation gene sequencing with genetic manipulation of model organisms, custom-synthesized fluorescent molecular probes for monitoring physiological/pathological processes in model organisms in vivo, and microfluidic systems for manipulation of model organisms and monitoring of biochemical pathways in vivo. A key innovative element of this proposal is the creation of three core facilities that are designed to operate synergistically: imaging of model organisms treated with fluorescent probes developed by one core facility will be facilitated by the use of microfabricated devices developed in a second core facility; screening of mutant organisms such as C. elegans and zebrafish against these probes will be used to discover novel disease-related phenotypes that can be precisely mapped to identify specific targets through the next generation genomic sequencing and related genomic technologies offered by a third core facility. The proposed Center will exploit the strengths of KU and associated universities in the areas of genetics, bioanalytical chemistry, bioengineering, and chemical synthesis and will create new methodologies and approaches that can be used to investigate any pathway involved in disease. These new technologies will be disseminated through research collaborations, publications, and potential commercialization.